Sequentially cross-linked polyethylene

ABSTRACT

A method of producing an improved polyethylene, especially an ultra-high molecular weight polyethylene utilizes a sequential irradiation and annealing process to form a highly cross-linked polyethylene material. The use of sequential irradiation followed by sequential annealing after each irradiation allows each dose of irradiation in the series of doses to be relatively low while achieving a total dose which is sufficiently high to cross-link the material. The process may either be applied to a preformed material such as a rod or bar or sheet made from polyethylene resin or may be applied to a finished polyethylene part. If applied to a finished polyethylene part, the irradiation and annealing must be accomplished with the polyethylene material not in contact with oxygen at a concentration greater than 1% oxygen volume by volume. When applied to a preform, such as a rod, the annealing of the bulk polymer part of the rod from which the finished part is made must take place on the rod before the implant is machined therefrom and exposed to oxygen.

CROSS-REFERENCED TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/315,994 filed on Dec. 9, 2008 which is a continuation of U.S.application Ser. No. 10/957,782 filed on Oct. 4, 2007 now U.S. Pat. No.7,517,919 which is a continuation of U.S. application Ser. No.10/454,815 filed on Jun. 4, 2003 which claimed the benefit of the filingdate of U.S. Provisional Patent Application No. 60/386,660 filed Jun. 6,2002, the disclosures of which are hereby incorporated herein byreference.

BACKGROUND OF THE INVENTION

This invention relates to medical implants formed of a polymericmaterial such as ultra-high molecular weight polyethylene, with superioroxidation and wear resistance produced by a sequential irradiation andannealing process.

Various polymer systems have been used for the preparation of artificialprostheses for biomedical use, particularly orthopedic applications.Among them, ultra-high molecular weight polyethylene is widely used forarticulation surfaces in artificial knee, hip, and other jointreplacements. Ultra-high molecular weight polyethylene (UHMWPE) has beendefined as those linear polyethylenes which have a relative viscosity of2.3 or greater at a solution concentration of 0.05% at 135° C. indecahydronaphthalene. The nominal weight—average molecular weight is atleast 400,000 and up to 10,000,000 and usually from three to sixmillion. The manufacturing process begins with the polymer beingsupplied as fine powder which is consolidated into various forms, suchas rods and slabs, using ram extrusion or compression molding.Afterwards, the consolidated rods or slabs are machined into the finalshape of the orthopedic implant components. Alternatively, the componentcan be produced by compression molding of the UHMWPE resin powder.

All components must then go through a sterilization procedure prior touse, but usually after being packaged. There exists severalsterilization methods which can be utilized for medical applications,such as the use of ethylene oxide, gas plasma, heat, or radiation.However, applying heat to a packaged polymeric medical product candestroy either the integrity of the packaging material (particularly theseal, which prevents bacteria from going into the package after thesterilization step) or the product itself.

It has been recognized that regardless of the radiation type, the highenergy beam causes generation of free radicals in polymers duringradiation. It has also been recognized that the amount or number of freeradicals generated is dependent upon the radiation dose received by thepolymers and that the distribution of free radicals in the polymericimplant depends upon the geometry of the component, the type of polymer,the dose rate, and the type of radiation beam. The generation of freeradicals can be described by the following reaction (which usespolyolefin and gamma ray irradiation for illustration):

Depending on whether or not oxygen is present, primary free radicals r·will react with oxygen and the polymer according to the followingreactions as described in “Radiation Effects on Polymers,” edited byRoger L. Clough and Shalaby W. Shalaby, published by American ChemicalSociety, Washington, D.C., 1991.

In the presence of oxygen

In radiation in air, primary free radicals r· will react with oxygen toform peroxyl free radicals r0₂·, which then react with polyolefin (suchas UHMWPE) to start the oxidative chain scission reactions (reactions 2through 6). Through these reactions, material properties of the plastic,such as molecular weight, tensile and wear properties, are degraded.

It has been found that the hydroperoxides (rOOH and POOH) formed inreactions 3 and 5 will slowly break down as shown in reaction 7 toinitiate post-radiation degradation. Reactions 8 and 9 representtermination steps of free radicals to form ester or carbon-carboncross-links. Depending on the type of polymer, the extent of reactions 8and 9 in relation to reactions 2 through 7 may vary. For irradiatedUHMWPE, a value of 0.3 for the ratio of chain scission to cross-linkinghas been obtained, indicating that even though cross-linking is adominant mechanism, a significant amount of chain scission occurs inirradiated polyethylene.

By applying radiation in an inert atmosphere, since there is no oxidantpresent, the primary free radicals r· or secondary free radicals P· canonly react with other neighboring free radicals to form carbon-carboncross-links, according to reactions 10 through 12 below. If all the freeradicals react through reactions 10 through 12, there will be no chainscission and there will be no molecular weight degradation. Furthermore,the extent of cross-linking is increased over the original polymer priorto irradiation. On the other hand, if not all the free radicals formedare combined through reactions 10, 11 and 12, then some free radicalswill remain in the plastic component.

In an Inert Atmosphere

r·+polyolefin . . . P·  (10)

2r· . . . r-r(C-C cross-linking)  (11)

2P· . . . P-P(C-C cross-linking)  (12)

It is recognized that the fewer the free radicals, the better thepolymer retains its physical properties over time. The greater thenumber of free radicals, the greater the degree of molecular weight andpolymer property degradation will occur. Applicant has discovered thatthe extent of completion of free radical cross-linking reactions isdependent on the reaction rates and the time period given for reactionto occur.

UHMWPE is commonly used to make prosthetic joints such as artificial hipjoints. In recent years, it has been found that tissue necrosis andinterface osteolysis may occur in response to UHMWPE wear debris. Forexample, wear of acetabular cups of UHMWPE in artificial hip joints mayintroduce microscopic wear particles into the surrounding tissues.

Improving the wear resistance of the UHMWPE socket and, thereby,reducing the rate of production of wear debris may extend the usefullife of artificial joints and permit them to be used successfully inyounger patients. Consequently, numerous modifications in physicalproperties of UHMWPE have been proposed to improve its wear resistance.

It is known in the art that ultrahigh molecular weight polyethylene(UHMWPE) can be cross-linked by irradiation with high energy radiation,for example gamma radiation, in an inert atmosphere or vacuum. Exposureof UHMWPE to gamma irradiation induces a number of free-radicalreactions in the polymer. One of these is cross-linking. Thiscross-linking creates a 3-dimensional network in the polymer whichrenders it more resistant to adhesive wear in multiple directions. Thefree radicals formed upon irradiation of UHMWPE can also participate inoxidation which reduces the molecular weight of the polymer via chainscission, leading to degradation of physical properties, embrittlementand a significant increase in wear rate. The free radicals are verylong-lived (greater than eight years), so that oxidation continues overa very long period of time resulting in an increase in the wear rate asa result of oxidation over the life of the implant.

Sun et al. U.S. Pat. No. 5,414,049, the teachings of which areincorporated herein by reference, broadly discloses the use of radiationto form free radicals and heat to form cross-links between the freeradicals prior to oxidation.

Hyon et al. U.S. Pat. No. 6,168,626 relates to a process for formingoriented UHMWPE materials for use in artificial joints by irradiatingwith low doses of high-energy radiation in an inert gas or vacuum tocross-link the material to a low degree, heating the irradiated materialto a temperature at which compressive deformation is possible,preferably to a temperature near the melting point or higher, andperforming compressive deformation followed by cooling and solidifyingthe material. The oriented UHMWPE materials have improved wearresistance. Medical implants may be machined from the oriented materialsor molded directly during the compressive deformation step. Theanisotropic nature of the oriented materials may render them susceptibleto deformation after machining into implants.

Salovey et al. U.S. Pat. No. 6,228,900, the teachings of which areincorporated by reference, relates to a method for enhancing thewear-resistance of polymers, including UHMWPE, by cross-linking them viairradiation in the melt.

Saum et al. U.S. Pat. No. 6,316,158 relates to a process for treatingUHMWPE using irradiation followed by thermally treating the polyethyleneat a temperature greater than 150° C. to recombine cross-links andeliminate free radicals.

Several other prior art patents attempt to provide methods which enhanceUHMWPE physical properties. European Patent Application 0 177 522 81relates to UHMWPE powders being heated and compressed into ahomogeneously melted crystallized morphology with no grain memory of theUHMWPE powder particles and with enhanced modulus and strength. U.S.Pat. No. 5,037,928 relates to a prescribed heating and cooling processfor preparing a UHMWPE exhibiting a combination of properties includinga creep resistance of less than 1% (under exposure to a temperature of23° C. and a relative humidity of 50% for 24 hours under a compressionof 1000 psi) without sacrificing tensile and flexural properties. U.K.Patent Application GB 2 180 815 A relates to a packaging method where amedical device which is sealed in a sterile bag, afterradiation/sterilization, is hermetically sealed in a wrapping member ofoxygen-impermeable material together with a deoxidizing agent forprevention of post-irradiation oxidation.

U.S. Pat. No. 5,153,039 relates to a high density polyethylene articlewith oxygen barrier properties. U.S. Pat. No. 5,160,464 relates to avacuum polymer irradiation process.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to a method for providing a polymericmaterial, such as UHMWPE, with superior oxidation resistance, mechanicalstrength and wear properties. For the purpose of illustration, UHMWPEwill be used as an example to describe the invention. However, all thetheories and processes described hereafter should also apply to otherpolymeric materials such as polypropylene, high density polyethylene,polyhydrocarbons, polyester, nylon, polyurethane, polycarbonates andpoly(methylmethcrylate) unless otherwise stated. The method involvesusing a series of relatively low doses of radiation with an annealingprocess after each dose.

As stated above, UHMWPE polymer is very stable and has very goodresistance to aggressive media except for strong oxidizing acids. Uponirradiation, free radicals are formed which cause UHMWPE to becomeactivated for chemical reactions and physical changes. Possible chemicalreactions include reacting with oxygen, water, body fluids, and otherchemical compounds while physical changes include density,crystallinity, color, and other physical properties. In the presentinvention, the sequential radiation and annealing process greatlyimproves the physical properties of UHMWPE when compared to applying thesame total radiation dose in one step. Furthermore, this process doesnot employ stabilizers, antioxidants, or any other chemical compoundswhich may have potentially adverse effects in biomedical or orthopedicapplications.

It is also known that at relatively low dose levels (<5 MRads) ofirradiation residual free radicals are mostly trapped in the crystallineregion while most free radicals crosslink in the amorphous region. Thereis a steep free radical concentration gradient across thecrystalline-amorphous boundary, which provides a significant drivingforce for free radicals to diffuse into the amorphous region where theycan crosslink upon subsequent annealing. However, if the polyethylene isallowed to continuously accumulate higher radiation doses withoutinterruptive annealing, molecules in the amorphous region become moreand more stiffened due to increased crosslinking. As a result, theamorphous region traps more and more free radicals. This leads to adiminished free radical gradient across the crystalline-amorphousboundary, thereby reducing the driving force for free radical diffusionupon subsequent annealing. By limiting the incremental dose to below 5MRads and preferably below 3.5 MRads and following with annealing, arelatively higher free radical diffusion driving force can bemaintained, allowing a more efficient free radical reduction uponannealing. If higher radiation doses are used, there could becross-linking at the chain folded crystal surfaces. This could hamperthe movement of free radicals from the crystal to the amorphous regions.

It has been found that polyethylene crystallinity increases continuouslywith increasing radiation-doses due to chain-scission (approximately 55%before radiation, increasing to 60% at 3.0 MRads, and to 65% at 10MRads).

As the crystallinity increases with increasing dose of radiation, moreresidual free radicals are created and stored in the extra crystallineregions, which makes it increasingly more difficult to eliminate freeradicals by annealing below the melt temperature. However, treatingabove the melting temperature (re-melting) significantly alters thecrystallinity and crystal morphology which leads to significantreduction in mechanical properties such as yield strength and ultimatetensile strength and creep resistance and these properties are importantfor the structural integrity of the implant.

An orthopedic preformed material such as a rod, bar or compressionmolded sheet for the subsequent production of a medical implant such asan acetabular or tibial implant with improved wear resistance is madefrom a polyethylene material cross-linked at least twice by irradiationand thermally treated by annealing after each irradiation. The materialis cross-linked by a total radiation dose of from about 2 MRads to 100MRads and preferably between 5 MRads and 10 MRads. The incremental dosefor each irradiation is between about 2 MRads and about 5 MRads. Theweight average molecular weight of the material is over 400,000.

The annealing takes place at a temperature greater than 25° C.,preferably between 110° C. and 135° C. but less than the melting point.Generally, the annealing takes place for a time and temperature selectedto be at least equivalent to heating the irradiated material at 50° C.for 144 hours as defined by Arrenhius' equation 14. The material isheated for at least about 4 hours and then cooled to room temperaturefor the subsequent irradiation in the series.

By limiting the incremental dose to below 5 MRads and preferably below3.5 MRads and following with annealing, the crystallinity will fluctuatebetween 55% and 60% (instead of 55-65%) and hence both the amount ofchain-scission and residual free-radical concentration can besignificantly reduced.

The polyethylene of the present invention may be in the form of apreformed rod or sheet with a subsequent production of a medical implantwith improved wear resistance. The preformed rod or sheet iscross-linked at least twice by irradiation and thermally treated byannealing after each radiation. The incremental dose for each radiationis preferably between about 2 and 5 MRads with the total dose between 2and 100 MRads and preferably between 5 and 10 MRads.

After each irradiation, the preformed material is annealed either in airor in an inner atmosphere at a temperature of greater than 25° C. andpreferably less than 135° C. or the melting point. Preferably, theannealing takes place for a time and temperature selected to be at leastequivalent to heating the irradiated material at 50° C. for 144 hours asdefined by Arrenhius' equation (14). Generally, each heat treatmentlasts for at least 4 hours and preferably about 8 hours.

The preformed polyethylene material is then machined into a medicalimplant or other device. If the irradiation process occurred in air,then the entire outer skin to about 2 mm deep is removed from thepreform prior to machining the medical implant or other device. If theprocess was done in a vacuum or an inner atmosphere such a nitrogen,then the outer skin may be retained.

The end-results of reduced chain-scission and free-radical concentrationare improved mechanical properties, improved oxidation resistance andenhanced wear resistance.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the oxidation index profiles of the specimens of Example 8;and

FIG. 2 shows the oxidation index profiles of the specimens of Example11.

DETAILED DESCRIPTION

Abbreviations used in this application are as follows:

UHMW—ultra-high molecular weight

UHMWPE—ultra-high molecular weight polyethylene

HMW—high molecular weight

HMWPE—high molecular weight polyethylene

This invention provides a method for improving the wear resistance of apolymer by crosslinking (preferably the bearing surface of the polymer)and then thermally treating the polymer, and the resulting polymer.Preferably, the most oxidized surface of the polymer is also removed.Also presented are the methods for using the polymeric compositions formaking products and the resulting products, e.g., in vivo implants.

The method of the invention utilizes at least two separate irradiationsfor crosslinking a polymer followed by a like number of thermaltreatments to decrease the free radicals to produce either a treatedfully formed or a preformed polymeric composition. The term “preformedpolymeric composition” means that the polymeric composition is not in afinal desired shape or from (i.e., not a final product). For example,where the final product of the preformed polymeric composition is anacetabular cup, the at least two irradiations and thermal treatments ofthe polymer could be performed at pre-acetabular cup shape, such as whenthe preformed polymeric composition is in the form of a solid bar orblock. Of course, the process of the present invention could be appliedto a fully formed implant if the process is done with the implant in anoxygen reduced atmosphere.

In the present invention, the wear resistance of a polymer is improvedby crosslinking. The crosslinking can be achieved by various methodsknown in the art, for example, by irradiation from a gamma radiationsource or from an electron beam, or by photocrosslinking. The preferredmethod for crosslinking the polymer is by gamma irradiation. The polymeris preferably crosslinked in the form of an extruded bar or moldedblock.

In the preferred method, the crosslinked polymer is subjected to thermaltreatment such as by annealing (i.e. heated above at or below themelting temperature of the crosslinked polymer) to produce the preformedpolymeric composition.

In the preferred embodiment of the invention, the outer layer of theresulting preformed polymeric composition, which is generally the mostoxidized and least crosslinked and, thus, least wear resistant, isremoved. For example, the bearing surface of the preformed polymericcomposition may be fashioned from inside, e.g., by machining away thesurface of the irradiated and thermally treated composition before orduring fashioning into the final product, e.g., into an implant. Bearingsurfaces are surfaces which are in moving contact, e.g., in a sliding,pivoting, or rotating relationship to one another.

High molecular weight (HMW) and ultra-high molecular weight (UHMW)polymers are preferred, such as HMW polyethylene (HMWPE), UHMWpolyethylene (UHMWPE), and UHMW polypropylene. HMW polymers havemolecular weights ranging from about 10⁵ grams per mole to just below10⁶. UHMW polymers have molecular weights equal to or higher than 10⁶grams per mole, preferably from 10⁶ to about 10⁷. The polymers aregenerally between about 400,000 grams per mole to about 10,000,000 andare preferably polyolefinic materials.

For implants, the preferred polymers are those that are wear resistantand have exceptional chemical resistance. UHMWPE is the most preferredpolymer as it is known for these properties and is currently widely usedto make acetabular cups for total hip prostheses and components of otherjoint replacements. Examples of UHMWPE are those having molecular weightranging from about 1 to 8×10⁶ grams per mole, examples of which are: GUR1150 or 1050 (Hoechst-Celanese Corporation, League City, Tex.) with aweight average molecular weight of 5 to 6×10⁶ grams per mole; GUR 1130with a weight average molecular weight of 3 to 4×10⁶; GUR 1120 or 1020with a weight average molecular weight of 3 to 4×10⁶; RCH 1000(Hoechst-Celanese Corp.) with a weight average of molecular weight of4×10⁶ and HiFax 1900 of 2 to 4×10⁶ (HiMont, Elkton, Md.). Historically,companies which make implants have used polyethylenes such as HIFAX1900, GUR 1020, GUR 1050, GUR 1120 and GUR 1150 for making acetabularcups.

Sterilization Methods: All polymeric products must be sterilized by asuitable method prior to implanting in the human body. For the formedcrosslinked and thermally treated polymeric compositions (i.e., thefinal products) of the present invention, it is preferable that theproducts be sterilized by a non-radiation based method, such as ethyleneoxide or gas plasma, in order not to induce additional crosslinking freeradicals and/or oxidation of the previously treated preformed polymericcomposition. Compared to radiation sterilization, a non-radiationsterilization method has a minor effect on the other important physicalcharacteristics of the product.

The degree of crystallinity can be determined using methods known in theart, e.g. by differential scanning calorimetry (DSC), which is generallyused to assess the crystallinity and melting behavior of a polymer.Wang, X. & Salovey, R., J. App. Polymer Sci., 34:593-599 (1987).

Wide-angle X-ray scattering from the resulting polymer can also be usedto further confirm the degree of crystallinity of the polymer, e.g. asdescribed in Spruiell, J. E., & Clark, E. S., in “Methods ofExperimental-Physics,” L. Marton & C. Marton, Eds., Vol. 16, Part B,Academic Press, New York (1980). Other methods for determining thedegree of crystallinity of the resulting polymer may include FourierTransform Infrared Spectroscopy (FTIR), e.g., as described in “FourierTransform Infrared Spectroscopy And Its Application To PolymericMaterials,” John Wiley and Sons, New York, U.S.A. (1982)} and densitymeasurement (ASTM D1505-68). Measurements of the gel content andswelling are generally used to characterize crosslink distributions inpolymers; the procedure is described in Ding, Z. Y., et al., J. PolymerSci., Polymer Chem., 29:1035-38 (1990). FTIR can also be used to assessthe depth profiles of oxidation as well as other chemical changes suchas unsaturation {Nagy, E. V. & Li, S., “A Fourier transform infraredtechnique for the evaluation of polyethylene orthopedic bearingmaterials,” Trans. Soc. for Biomaterials, 13:109 (1990); Shinde, A. &Salovey, R., J. Polymer Sci., Polm. Phys. Ed., 23:1681-1689 (1985)}.

Another aspect of the invention presents a process for making implantsusing the preformed polymeric composition of the present invention. Thepreformed polymeric composition may be shaped, e.g., machined, into theappropriate implants using methods known in the art. Preferably, theshaping process, such as machining, removing the oxidized surface of thecomposition.

The preformed polymeric compositions of the present invention can beused in any situation where a polymer, especially UHMWPE, is called for,but especially in situations where high wear resistance is desired. Moreparticularly, these preformed polymeric compositions are useful formaking implants.

An important aspect of this invention presents implants that are madewith the above preformed polymeric compositions or according to themethods presented herein. In particular, the implants are produced frompreformed polymeric composition made of UHMWPE irradiated andcrosslinked at least twice each time followed by annealing and thenremoving the oxidized surface layer and then fabricating into a finalshape. The preformed polymeric composition of the present invention canbe used to make the acetabular cup, or the insert or liner of the cup,or trunnion bearings (e.g. between the modular head and the hip stem).In the knee joint, the tibial plateau (femoro-tibial articulation), thepatellar button (patello-femoral articulation), and/or other bearingcomponents, depending on the design of the artificial knee joint. Thesewould include application to mobile bearing knees where articulationbetween the tibial insert and tibial tray occurs. In the shoulder, theprocess can be used in the glenoid component. In the ankle joint, thepreformed polymeric composition can be used to make the talar surface(tibiotalar articulation) and other bearing components. In the elbowjoint, the preformed polymeric composition can be used to make theradio-humeral joint, ulno-humeral joint, and other bearing components.In the spine, the preformed polymeric composition can be used to makeintervertebral disk replacement and facet joint replacement. Thepreformed polymeric composition can also be made into temporo-mandibularjoint (jaw) and finger joints. The above are by way of example, and arenot meant to be limiting.

The following discusses the first and second aspects of the invention inmore detail.

First Aspect of the Invention: Polymeric Compositions with IncreasedWear Resistance.

The first aspect of the invention provides preformed polymericcompositions which are wear resistant and useful for making in vivoimplants. In this aspect, for polymers in general, and more preferablyUHMW and HMW polymers, and most preferably UHMWPE and HMWPE, the atleast two (2) incremental irradiation doses are preferably from about 1to about 100 Mrad, and more preferably, from about 2 to about 5 Mrad.This most preferable range is based on achieving a reasonable balancebetween improved wear resistance and minimal degradation of otherimportant physical properties. The total dose is between 2 and 100 MRadand more preferably 5 to about 10 MRads.

In vivo implants of the present invention, i.e., irradiated within theabove dose ranges are expected to function in vivo without mechanicalfailure. The UHMWPE acetabular cups used by Oonishi et al. [in Radiat.Phys. Chem., 39:495-504 (1992)] were irradiated to 100 Mrad andfunctioned in vivo without reported mechanical failure as long as 26years of clinical use. Furthermore, it is surprising that, as shown inthe EXAMPLES, acetabular cups from the preformed polymeric compositionprepared according to the present invention, but irradiated to much lessthan 100 Mrad, exhibited much higher wear resistance than reported byOonishi et al.

On the other hand, if a user is primarily concerned with reducing wear,and other physical properties are of secondary concern, then a higherdose than the above stipulated most preferable range (e.g., 5 to 10Mrad) may be appropriate, or vice versa (as illustrated in the detailedexamples in the following section). The optimum radiation dose ispreferably based on the total dose received at the level of the bearingsurface in the final product. Gamma radiation is preferred.

The preferred annealing temperature after each sequential irradiation isbelow the melting temperature of the UHMWPE which is generally below135° C.

The annealing temperature is preferably from about room temperature tobelow the melting temperature of the irradiated polymer; more preferablyfrom about 90° C. to about 1° C. below the melting temperature of theirradiated polymer; and most preferably from about 110° C. to about 130°C. For example, UHMWPE may be annealed at a temperature from about 25°C. to about 140° C., preferably from about 50° C. to about 135° C. andmore preferably from about 80° C. to about 135° C. and most preferablybetween 110° C. to 130° C. The annealing period is preferably from about2 hours to about 7 days, and more preferably from about 7 hours to about5 days and most preferably from about 10 hours to about 24 hours.

Instead of using the above range of radiation dose as a criterion, theappropriate amount of crosslinking may be determined based on the degreeof swelling, gel content, or molecular weight between crosslinks afterthermal treatment. This alternative is based on the applicant's findings(detailed below) that acetabular cups made from UHMWPE falling within apreferred range of these physical parameters have reduced ornon-detectable wear. The ranges of these physical parameters include oneor more of the following: a degree of swelling of between about 1.7 toabout 5.3; molecular weight between crosslinks of between about 400 toabout 8400 g/mol; and a gel content of between about 95% to about 99%. Apreferred polymer or final product has one or more, and preferably all,of the above characteristics. These parameters can also be used asstarting points in the second aspect of the invention (as illustrated bythe flowchart, discussed below) for determining the desired radiationdose to balance the improvement in wear resistance with other desiredphysical or chemical properties, such as polymer strength or stiffness.

After crosslinking and thermal treatment, preferably, the most oxidizedsurface of the preformed polymeric composition is removed. The depthprofiles of oxidation of the preformed polymeric composition can bedetermined by methods known in the art, such as FTIR. In general, themost oxidized surface of preformed polymeric composition which isexposed to air is removed, e.g. by machining, before or while fashioningthe preformed polymeric composition into the final product. Since oxygendiffuses through the polyethylene with time, the sequentialirradiation/annealing preferably should be completed prior to oxygendiffusing in high concentrations to the area of the preform from whichthe final part is made.

As noted above, the most preferable range of total dose for crosslinkingradiation (i.e., from 5 to 10 Mrad) was based on Wang et al. “TribologyInternational” Vol. 3, No. 123 (1998) pp. 17-35. After irradiation inair the gap in time before annealing is preferably seven days but atleast before any oxygen diffuses into the area of the rod from which theimplant is made. It has been found that it takes at least seven days todiffuse through the surface layer.

Free radicals generated during an irradiation step should be reduced toan acceptable level by annealing before exposure to oxygen. The portionof the material from which the implant is made contains free radicalsand if it is exposed to air or other oxidants after the manufacturingprocess, oxidation will occur. The bulk portion of the polymer fromwhich the implant is to be made should be annealed at an elevatedtemperature while out of contact with oxygen for a prescribed time. Thisis because the rate of free radical reactions (reactions 10 through 12)increases with increasing temperature, according to the followinggeneral expressions:

$\begin{matrix}{\frac{{r} \cdot}{t} = {{{k_{1}\lbrack {r \cdot} \rbrack}\mspace{14mu} {and}\mspace{14mu} \frac{{P} \cdot}{t}} = {k_{2}\lbrack {P \cdot} \rbrack}}} & (13)\end{matrix}$

Compared to room temperature, an elevated temperature not only increasesthe reaction rate constants, k₁ and k₂, but also helps free radicals r·and P· to migrate in the plastic matrix to meet other neighboring freeradicals for cross-linking reactions. In general, the desired elevatedtemperature is between room temperature to below the melting point ofthe polymer. For UHMWPE, this temperature range is between about 25° C.and about 140° C. It is to be noted that the higher the temperatureused, the shorter the time period needed to combine free radicals.Additionally, due to the high viscosity of a UHMWPE melt, the formedUHMWPE often contains residual (internal) stress caused by incompleterelaxation during the cooling process, which is the last step of theforming process. The annealing process described herein will also helpto eliminate or reduce the residual stress. A residual stress containedin a plastic matrix can cause dimensional instability and is in generalundesirable.

In the preferred embodiment, the sequential irradiation followed bysequential annealing after each irradiation is preformed in air on apreform such as an extruded rod, bar or compression molded sheet madefrom polyethylene and preferably UHMWPE. Obviously, the final sequentialannealing must take place prior to the bulk material of the final partor implant being exposed to air. Normally, it takes at least seven daysfor atmospheric oxygen to diffuse through the outer layer ofpolyethylene and deeply enough into rod, bar or sheet to effect the bulkpolyethylene forming the final part. Therefore, the last annealing inthe sequence preferably should take place prior to the time required forthe oxygen to diffuse deeply into the rod. Of course, the more materialwhich must be machined off to reach the finished part, the longer onecan wait for the completion of the sequential irradiation and annealingprocess.

If the sequential irradiation/annealing process is performed on a finalproduct, such as an acetabular cup, after machining, the polymericcomponent is preferably packaged in an air tight package in anoxidant-free atmosphere, i.e. less than 1% volume by volume. Thus, allair and moisture must be removed from the package prior to the sealingstep. Machines to accomplish this are commercially available, such asfrom Orics Industries Inc., College Point, N.Y., which flush the packagewith a chosen inert gas, vacuum the container, flush the container forthe second time, and then heat seal the container with a lid. Ingeneral, less than 0.5% (volume by volume) oxygen concentration can beobtained consistently. An example of a suitable oxidant impermeable (airtight) packaging material is polyethylene terephthalate (PET). Otherexamples of oxidant impermeable packaging material is poly(ethylenevinyl alcohol) and aluminum foil, whose oxygen and water vaportransmission rates are essentially zero. All these materials arecommercially available. Several other suitable commercial packagingmaterials utilize a layer structure to form a composite material withsuperior oxygen and moisture barrier properties. An example of this typeis a layered composite comprised of polypropylene/poly(ethylene vinylalcohol)/polypropylene.

With a final product, following each irradiation step, the heattreatment or annealing step should be performed while the implant is outof contact with oxygen or in an inert atmosphere and at an elevatedtemperature to cause free radicals to form cross-links withoutoxidation. If proper packaging materials and processes are used andoxidant transmission rates are minimal, then the oxidant-free atmospherecan be maintained in the package and a regular oven with air circulationcan be used for heat treatment after sterilization. To absolutely ensurethat no oxidants leak into the package, the oven may be operated under avacuum or purged with an inert gas. In general, if a higher temperatureis used, a shorter time period is required to achieve a prescribed levelof oxidation resistance and cross-linking. In many cases, therelationship between the reaction temperature and the reaction ratefollows the well-known Arrhennius equation:

k ₁ or k ₂ =A*exp(−ΔH/RT)  (14)

where k₁ and k₂ are reaction rate constants from reactions 13 and 14

A is a reaction dependent constant

ΔH is activation energy of reaction

T is absolute temperature (K)

R is the universal gas constant.

It is very important to ensure that the number of free radicals has beenreduced to a minimal or an accepted level by the heat treatment. This isbecause the presence of an oxidant causes not only the oxidation ofpre-existing free radicals, but also the formation of new free radicalsvia reactions 2 through 7. When the number of free radicals grows, theextent of oxidation and the oxidation rate will increase according tothe following equations:

$\begin{matrix}{\frac{{r} \cdot}{t} = {{{{k_{3}\lbrack {r \cdot} \rbrack}\lbrack O_{2} \rbrack}\mspace{14mu} {and}\mspace{14mu} \frac{{P} \cdot}{t}} = {{k_{4}\lbrack {P \cdot} \rbrack}\lbrack O_{2} \rbrack}}} & (15)\end{matrix}$

Where free radicals r· and P· can grow in number in the presence ofoxidants and in turn increase the oxidation rates. It is also to benoted that the oxidation reaction rate constants k₃ and k₄ increase withincreasing temperature, similar to k₁ and k₂. Therefore, to determine ifa certain level of residual free radicals is acceptable or not, it isrequired to evaluate specific material properties after the plasticsample is stored or aged at the application temperature for a timeperiod which is equal to or longer than the time period intended for theapplication of the plastic component. An alternative to the method toassess the aging effect is to raise the aging temperature of the plasticsample for a shorter time period. This will increase the reaction rateconstants k₃ and k₄ significantly and shorten the aging time. It hasbeen found that an acceptable level of residual free radicals is1.0×10¹⁷/g for UHMWPE use for orthopedic implants.

Example I

As stated above, the ultra-high molecular weight polyethylene extrudedrod is irradiated for a sufficient time for an accumulated incrementaldose of between 2 and 5 (MRads) (20 to 50 kGy). After this irradiationstep, the extruded rod is annealed in air preferably at a temperaturebelow its melting point, preferably at less than 135° C. and morepreferably between 110° C. and 130° C. The irradiation and annealingsteps are then repeated two or more times so that the total radiationdose is between 4 and 15 MRads (50 to 150 kGy). In this example, the rodis irradiated for a total dose of 3 MRad and then annealed at 130° C.for 24 hours, allowed to cool to room temperature and sit for 3 days andthen reirradiated for a dose of 3.0 MRads (a total dose of 6 MRads)again annealed at 130° C. for 24 hours, allowed to cool at roomtemperature and sit for an additional 3 days and then irradiated a thirdtime with a 3.0 MRad dose (for a total of 9 MRads) and again annealed at130° C. for 24 hours. The rod is cooled to room temperature and is thenmoved into the manufacturing process which forms the orthopedic implantby machining.

The above example can also be applied to compression molded sheet with,for example, a tibial component being manufactured out of thesequentially irradiated and annealed material.

In the preferred embodiment, the total radiation dose can be anywherebetween 5 and 15 MRads and most preferably 9 MRads applied in threedoses of 3 MRads, as done in the above example. The length of timebetween sequential irradiation is preferably between 3 to 7 days. Whilethe annealing step is preferably performed after the irradiation step,it is possible to heat the rod to the annealing temperatures andirradiate it sequentially in the heated state. The rod may be allowed tocool between doses or can be maintained at the elevated temperatures forthe entire series of doses.

Example II

A machined tibial implant in its final form is packaged in an oxygenreduced atmosphere having an oxygen concentration less than 1% volume byvolume. The packaged implant is then processed as described in Example Ithrough a series of three (3) irradiation and annealing cycles asdescribed above with the total radiation dose being 9 MRads. The implantwas then boxed and ready for final shipping and use.

Example III

Two ultra-high molecular weight polyethylene rods (one of compressionmolded GUR 1020 and the other of ram extruded GUR 1050) with across-section profile of 2.5-inch×3.5-inch (GUR 1020) and 3.5-inchdiameter (GUR 1050), respectively, were used. Lengths of these rods weresectioned into 18-inch lengths; three 18-inch rods (staggered andseparated by small paper boxes) were packaged in a paper carton beforethe sequential radiation process. The purpose of the packaging andstaggering was to reduce the possibility of blocking the radiation(gamma rays) to each individual rod during the process.

The rods went through the following sequential process in air:

1. Each rod received a nominal dose of 30 kGy gamma radiation;

2. Each was then annealed at 130° C. for 8 hours; and

3. Steps 1 and 2 were repeated two more times. Preferably, the repeatedsteps occurred within three days each.

While the process was done in air, it could be performed in an inertatmosphere such as nitrogen.

The rods received a nominal 90 kGy total dosage of gamma radiation afterthe completion of the above sequential process. The GUR 1020 rod isdesignated as sample “A” and the GUR 1050 rod as sample “B”. When donein air, 2 mm of the entire outer surface of each rod is removed afterthe entire process is complete.

Control—The following materials/process had been selected as “Control”:

1. The conventionally (in nitrogen or vacuum N₂VAC) processed molded GUR1020 and extruded GUR 1050 rods received in a single dose 30 kGy gammaradiation sterilization in nitrogen but no annealing and were designatedsamples “C” and “D,” respectively.

2. A GUR 1050 rod that received 90 kGy total dose (non-sequentially)followed by annealing at 130° C. for 8 hours and was designated assample “E”.

Tensile Test—The ASTM D 638 Type IV specimens were used for the tensileproperty evaluation of samples A-E. Tensile properties were determinedfrom the average of six (6) specimens. An Instron Model 4505 Test Systemwas used to conduct this evaluation. Crosshead speed was 5.0 mm/min. Theresults are listed in Table I.

Free Radical Concentration Measurement—All free radical measurement wasconducted before the accelerated aging treatment. The specimens are 3 mmdiameter, 10 mm long cylinders. This evaluation was carried out at theUniversity of Memphis (Physics Department). Free radical concentrationwas measured and calculated from average of three (3) specimens. Freeradical measurements were performed using electron spin resonancetechnique. This is the only technique that can directly detect freeradicals in solid and aqueous media. An ESR spectrometer (Bruker EMX)was used in this evaluation.

Oxidation Resistance Measurement—Oxidation index/profile measurement wasperformed after accelerated aging using the protocol per ASTM F 2003 (5atm O2 pressure at 70° C. for 14 days) on specimens machined into90×20×10 mm thick rectangular blocks from the center of the rods. Theoxidation analysis was performed on a Nicolet model 750 Magna-IR™spectrometer per ASTM F2102-01 using an aperture 100 μm×100 μm and 256scans. An oxidation index was defined by the ratio of the carbonyl peakarea (1660 to 1790 cm⁻¹) to the 1370 cm⁻¹ peak area (1330 to 1390 cm⁻¹).A through-the-thickness (10 mm) oxidation index profile is generatedfrom an average of three (3) specimens. The 0 and 10 mm depths representupper and lower surfaces of specimens. The maximum oxidation index ofeach specimen was used to determine if there was a significantdifference.

Statistical Analysis—Student's t Test—Test of Significance—A student's ttest (two-tail, unpaired) was conducted to measure statisticalsignificance at the 95% confidence level (p<0.05).

Tensile Test Results

TABLE 1 Comparison Of Tensile Properties, N = 6 Yield Ultimate StrengthStrength Elongation at Sample Material (MPa) (MPa) Break (%) A GUR 102024.9 ± 0.6 59.3 ± 1.5 301 ± 7 B GUR 1050 25.6 ± 0.4 54.8 ± 1.2 255 ± 7 CGUR 1020 25.2 ± 0.1 57.0 ± 2.3  372 ± 10 D GUR 1050 24.5 ± 0.2 56.4 ±4.0  370 ± 10 E GUR 1050 23.9 ± 0.4 51.0 ± 2.1 214 ± 5

The sequential process of samples “A” and “B” maintains both tensileyield and ultimate strength (when compared to their respectivecounterparts samples C and D). Consequently, the null hypothesis thatsequential process maintains (p=0.001) tensile strengths was verified.Results also indicated that a sequential process improved elongation atbreak in radiation-crosslinked GUR 1050 by 19% (p=0.001) over a processthat produced crosslinking by a single-dose delivery of 90 kGy(non-sequentially) and annealed at 130° C. for 8 hours (sample E).

The sequential crosslinking reduces free radical concentration inradiation-crosslinked GUR 1020 and 1050 by 87% (p=0.001) and 94%(p=0.001), respectively when comparing to their respective N2VAC™process counterparts, samples C and D. The sequential crosslinkingprocess also reduces free radical concentration in radiation-crosslinkedGUR 1050 by 82% (p=0.001) over a process that produced crosslinking by asingle-dose delivery of 90 kGy (non-sequentially) and annealed at 130°C. for 8 hours (sample E).

The sequential crosslinking process reduces the maximum oxidation indexin radiation crosslinked GUR 1020 and 1050 by 82% (p=0.001) and 86%(p=0.001), respectively (when compared to control samples C and D). Theprocess also reduces the maximum oxidation index inradiation-crosslinked GUR 1050 by 74% (p=0.001) over a process thatproduced crosslinking by a single-dose delivery of 90 kGy(non-sequentially) and annealed at 130° C. for at least 8 hours (sampleE). The sequential irradiation and annealing process maintains theoriginal tensile yield and ultimate strengths reduces free radicalconcentration and improves oxidation resistance. It is believed thatsequential cross-linking is a gentler process than a single doseprocess.

Furthermore, this process has significant benefits over a single-dosedelivery of 90 kGy (non-sequentially) and annealed at 130° C. for 8hours in at least three areas. First there is a lower free radicalconcentration, second a better oxidation resistance and third a bettertensile elongation.

While the preferred process is three sequential applications of 30 kGyeach followed by annealing at 130° C. for eight (8) hours, a two stepprocess of 30 kGy to 45 kGy radiation applied twice, each followed by anannealing at about 130° C. for about 8 hours may be used.

If it is desired to have an additional sterilization step after thesequential irradiation and annealing of the ultra-high molecular weightpolyethylene preformed part or packaged final part then the part may besterilized via non-irradiative methods such as ethylene oxide or gasplasma and then packaged or repackaged and shipped in the standardmanner.

Example IV Effect of Sequential Cross-Link Dose on the PhysicalProperties of UHMWPE

Materials and Methods—Medical-grade UHMWPE extruded bars (GUR 1050,Perplas Medical), with a weight average molecular weight of 5×10⁶Daltons and a diameter of 83 mm were used for all subsequent treatments.The GUR 1050 bars had a total original length of 5 meters and wereextruded from the same polymer and extrusion lots. These bars were cutinto 460 mm long sections and irradiated with gamma ray at roomtemperature in ambient air.

The treatments of these materials are listed in Table 3. Theterminologies 1× means a single cycle of irradiation and annealing and2× and 3× denote that the materials received the sequential cross-linkprocess, two and three times, respectively; these materials received anominal dose of 3.0 MRads during each step of radiation. Annealing wasdone at 130° C. for 8 hours after each radiation dose.

Differential Scanning Calorimetry (DSC)—DSC samples were cut frommachined 1 mm thick sheets. Specimens (˜4 mg) were heated from 50° C. atheating rate of 10 C/min in a Perkin-Elmer DSC 7 to 175° C. The meltingtemperature was determined from the peak of the melting endotherm. Theheat of fusion was calculated through an integration of the area underthe melting endotherm between 60° C. and 145° C. Crystallinity wascalculated using the abovementioned heat of fusion divided by 288 J/g,the heat of fusion of an ideal polyethylene crystal.

Results and Discussion—The measured melting temperature andcrystallinity are listed in Table 2. After the three consecutivesequential cross-link process; materials received 3.0, 6.0 and 9.0 MRadstotal gamma-radiation showed no change in crystallinity when comparingto material that received a 3.0 MRads gamma-radiation in a containerwith less than 0.5% oxygen (58% v 57.6%) while remelting caused asignificant decrease in crystallinity from 57% to 48%.

TABLE 2 Melting Temperature, Treatment ° C. Crystallinity, % NoRadiation 135.8 ± 0.1 54.3 ± 0.7 3.0 MRads single dose in a 139.9 ± 0.257.6 ± 0.8 Container with less than 0.5% oxygen 1X cross-linked and140.1 ± 0.2 56.7 ± 0.9 annealed one time, 3.0 MRads 2X sequentiallycross-link 141.1 ± 0.1 57.4 ± 0.6 and annealed, 6.0 MRads 3Xsequentially cross-link 142.3 ± 0.1 58.0 ± 0.9 and annealed, 9.0 MRads 5MRads single dose 137.0 ± 0.2 48.2 ± 0.7 cross-link, remelted at 150° C.for 8 hours 10 MRads single dose 139.7 ± 0.2 48.6 ± 0.6 cross-link,remelted at 150° C. for 8 hours

Example V Effect of Sequential Cross-link Dose on the Tensile Propertiesof UHMWPE

Materials and Methods—The materials for tensile property evaluation arethe same as the physical property materials described in Example IVabove. Six tensile specimens were machined out of the center of the 83mm diameter bars according to ASTM F648, Type IV and 1 mm thick. Tensileproperty evaluation was carried out on an electromechanical Instronmodel 4505 universal test frame at a speed of 50 mm/inch. The treatmentsof these materials are listed in Table 2.

Results and Discussion—The tensile properties (yield strength, ultimatestrength and elongation at break) are illustrated in Table 3. Thesequential cross-link process increased tensile yield strength followingeach treatment. This process also maintained ultimate tensile strengthin a cross-link UHMWPE while remelt processes significantly decreasedboth yield and ultimate strengths when comparing to samples thatreceived a 3.0 MRads gamma-radiation in a container with less than 0.5%oxygen.

TABLE 3 Yield Strength Ultimate Elongation at Treatment (MPa) Strength(MPa) Break (%) No radiation 21.4 ± 0.5 52.2 ± 3.1 380 ± 18 3.0 MRadssingle 24.5 ± 0.2 54.6 ± 4.0 356 ± 14 dose in a container with less than0.5% oxygen 1X cross-link and 22.7 ± 0.2 50.4 ± 2.8 338 ± 10 annealed, asingle time 3.0 MRads 2X sequentially 23.5 ± 0.5 52.2 ± 3.9 299 ± 11cross-link and annealed, 6.0 MRads total dose 3X sequentially 25.6 ± 0.454.8 ± 1.2 255 ± 7  cross-link and annealed, 9.0 MRads total dose 5MRads single dose 21.3 ± 0.3 48.2 ± 3.1 297 ± 8  cross-link, remelted at150° C. for 8 hours 10 MRads single 21.6 ± 0.4 43.6 ± 0.7 260 ± 12 dosecross-link remelted at 150° C. for 8 hours

Example VI Effect of Sequential Cross-link Dose on the Wear Propertiesof UHMWPE Acetabular Cups

Materials and Methods—Two types of UHMWPE materials, ram extruded GUR1050 bars (83 mm diameter) and compression molded GUR 1020 sheets (51mm×76 mm cross-section were treated). The sequential cross-link processwas performed on the GUR 1050 materials either 2 or 3 times and on GUR1020 material 3 times only. The nominal radiation dose for eachradiation/annealing cycle was 3.0 MRads. A current standard product,Trident™ design 32 mm acetabular cup (manufactured by HowmedicaOsteonics Corp. from GUR 1050 bar stock) sterilized under a 3.0 MRadsgamma-radiation in a container with less than 0.5% oxygen, was used as areference material.

All acetabular cups were fabricated according to prints for the Trident™design 32 mm insert (Howmedica Osteonics Corp. Cat. No. 620-0-32E). Thestandard cobalt chrome femoral heads (6260-5-132) were obtained, thesefemoral heads were of matching diameter to the insert inside diameter of32 mm.

An MTS 8-station hip simulator was used to perform the wear test. Thecups were inserted into metal shells as in vivo. The shells were thensecured into polyethylene holders that were in turn fitted ontostainless steel spigots. Each head was mounted onto a stainless steeltaper that was part of a reservoir containing a fluid serum media. Theserum reservoir was mounted on a 23-degree inclined block. A standardphysiological cyclic load between two peak loads of 0.64 and 2.5 kN at 1Hz was applied to all cups. This cyclic load was applied through thecentral axes of the cup, head and block.

The serum used for this test was a fetal-substitute alpha calf fractionserum (ACFS) diluted to a physiologically relevant value of about 20grams per liter of total protein. A preservative (EDTA) about 0.1 vol. %was added to minimize bacteria degradation. Each reservoir containedabout 450 milliliters of abovementioned ACFS with EDTA. This fluid inthe reservoir was replaced with fresh ACSS with EDTA every 250,000cycles. During the fluid replacement process, the samples were removedfrom the machine, cleaned and weighed.

Results and Discussion—The wear rate of each treatment is illustrated inTable 4; the measurement unit given is cubic millimeters per millioncycles (mm³/mc). The wear rate was corrected for the effect of fluidabsorption.

The cups subject to the 2× and 3× sequential cross-link processessignificantly reduced wear rate in UHMWPE acetabular cups by 86 to 96%when comparing to cups that received a 3.0 MRads gamma-radiation in acontainer with less than 0.5% oxygen.

TABLE 4 Wear Rate Reduction in Treatment (mm³/mc) Wear Rate (%) GUR 1050received 3.0 MRads 37.6 NA in a container with less than 0.5% oxygen (areference material) GUR 1050 received 2X 5.3 86 sequentially cross-linkand annealed, 6.0 MRads total GUR 1050 received 3X 1.4 96 sequentiallycross-link and annealed, 9.0 MRads total GUR 1020 received 3X 2.5 93sequentially cross-link and annealed, 9.0 MRads

Example VII Effect of Sequential Cross-link Dose on the Free RadicalConcentration in UHMWPE

Materials and Methods—The materials for free radical concentrationevaluated were:

1. GUR 1050 that received 3.0 MRads in a container with less than 0.5%oxygen (A reference material).

2. GUR 1050 that received 2× (6.0 MRads) sequentially cross-link andannealed.

3. GUR 1050 that received 3× (9.0 MRads) sequentially cross-link andannealed.

4. GUR 1050 that received a 9.0 MRads single total dose of cross-linkradiation and annealed at 130° C. for 8 hours.

The specimens are 3 mm diameter, 10 mm long cylinders fabricated fromabovementioned components. This evaluation was carried out at theUniversity of Memphis (Physics Department, Memphis, Tenn.). Free radicalconcentration was measured and calculated from an average of three (3)specimens. Free radical measurements were performed using electron spinresonance technique. This is the only technique that can directly detectfree radicals in solid and aqueous media. A top-of-the-line ESRspectrometer (Bruker EMX) was used in this evaluation.

Results and Discussion—The free radical concentration in the materialsis illustrated in Table 5; the measurement unit given is spins per grams(spins/g). The materials subjected to the 2× and 3× sequentialcross-link processes showed a significant reduction in free radicalconcentration about 94 to 98% when comparing to a GUR 1050 material thatreceived a 3.0 MRads gamma-radiation in a container with less than 0.5%oxygen. The materials subjected to the 2× and 3× sequential cross-linkprocesses also showed a significant reduction in free radicalconcentration about 82 to 92% when comparing to a GUR 1050 material thatreceived a 9.0 MRads total dose of gamma-radiation and annealed at 130°C. for 8 hours.

TABLE 5 Free Radical Reduction in Free Concentration Radical Treatment(10E+14 spins/g) Concentration (%) GUR 1050 received 3.0 MRads 204 ± 14NA in a container with less than 0.5% oxygen (a reference material) GUR1050 received 2X  5 ± 1 98 sequentially cross-link and annealed, 6.0MRads GUR 1050 received 3x 12 ± 1 94 sequentially cross-link andannealed, 9.0 MRads GUR 1050 received 9.0 MRads 67 ± 4 67 cross-link andannealed 130° C. for 8 hours

Example VIII Effect of Sequential Cross-link Dose on the OxidationResistance Property of UHMWPE

Materials and Methods—The materials for oxidation resistance evaluationwere:

1. GUR 1050 that received 3.0 MRads in a container with less than 0.5%oxygen (A reference material).

2. GUR 1050 that received 3× (9.0 MRads) sequentially cross-link andannealed.

3. GUR 1050 that received a 9.0 MRads single total dose of cross-linkradiation and annealed at 130° for 8 hours.

An accelerated aging protocol per ASTM F 2003 (5 atm oxygen pressure at70° C. for 14 days) was carried out at Exponent Failure AnalysisAssociates (Philadelphia, Pa.). The specimens were machined 90×20×10 mmrectangular blocks. The oxidation analysis was performed on a Nicoletmodel 750 Magna-IR™ spectrometer per ASTM F2102-01 using an aperture 100μm×100 μm and 256 scans. An oxidation index was defined by the ratio ofthe carbonyl peak area (1660 to 1790 cm⁻¹) to the 1370 cm⁻¹ peak area(1330 to 1390 cm⁻¹). A through-the-thickness (10 mm) oxidation indexprofile was generated from an average of three (3) specimens. The 0 and10 mm depths represented surfaces of specimens. The maximum oxidationindex of each specimen was used to determine if there was a significantdifference.

Results and Discussion—Oxidation index profiles and the maximumoxidation index are illustrated in FIG. 1 and Table 6, respectively. TheGUR 1050 materials subjected to the 3× sequential cross-link processshowed a significant reduction in both an oxidation index profile andmaximum oxidation index. The sequential cross-link process significantlyreduced the maximum oxidation index in 3× GUR 1050 by 86% when comparingto a GUR 1050 material that received a 3.0 MRads gamma-radiation in acontainer with less than 0.5% oxygen. The GUR 1050 materials subjectedto the 3× sequential cross-link process also showed a significantreduction in maximum oxidation index by 72% when comparing to a GUR 1050material that received a 9.0 MRads total dose of gamma-radiation andannealed at 130° C. for 8 hours.

TABLE 6 Treatment Maximum Oxidation Index GUR 1050 received 3.0 MRads ina 2.60 ± 0.02 container with less than 0.5% oxygen (a referencematerial) GUR 1050 received 3X sequentially 0.36 ± 0.02 cross-link andannealed, 9.0 MRads GUR 1050 received 9.0 MRads cross-link 1.29 ± 0.03and annealed 130° C. for 8 hours

Example IX Effect of Sequential Cross-link Dose on the Wear Propertiesof Direct Compression Molded UHMWPE Tibial Inserts

Materials and Methods—All direct compression molded (DCM) and machinedHowmedica Osteonics Corp. Scorpio® PS tibial inserts were fabricatedfrom GUR 1020 UHMWPE. DCM Scorpio® PS direct molded tibial inserts weretreated with the sequential cross-link process (radiation and annealing)two times (2×), a nominal dose of 4.5 MRads during each step ofradiation. The total accumulation of gamma-radiation in these componentswas 9.0 MRads. These components were packaged in an air impermeablepouch with less than 0.5% oxygen. Scorpio® PS tibial inserts (HowmedicaOsteonics Corp. Cat. No. 72-3-0708) were machined from compressionmolded GUR 1020 material and obtained from an in-house order. Thesecomponents then received gamma-radiation sterilization at a nominal doseof 3.0 MRads in a container with less than 0.5% oxygen. Wear test wasperformed on an MTS knee simulator according to an ISO standard 14243Part 3.

Results and Discussion—The wear test results are illustrated in Table 7;the measurement unit given is cubic millimeters per million cycles(mm³/mc). The wear rate was corrected for the effect of fluidabsorption. The DCM Scorpio® PS tibial inserts subjected to the 2× (4.5MRad) sequential cross-link process significantly reduced wear rate inUHMWPE tibial inserts by 88% when comparing to Scorpio® PS tibialinserts that received a 3.0 MRads gamma-radiation in a container withless than 0.5% oxygen.

TABLE 7 Wear Rate Reduction in Treatment (mm³/mc) Wear Rate (%)Scorpio ® PS machined from 32.6 ± 6.8  NA compression molded GUR 1020,received 3.0 MRads in a container with less than 0.5% oxygen (areference material) DCM Scorpio ® PS GUR 1020 3.8 ± 0.1 88 received 2X(4.5 MRads) sequentially cross-link and annealed, 9.0 MRads total

Example X Effect of Sequential Cross-link Dose on the Free RadicalConcentration in Direct Compression Molded UHMWPE Tibial Inserts

Materials and Methods—The materials for free radical concentrationevaluation are the same as the wear test materials described in ExampleIX, above. The specimens are 3 mm diameter, 10 mm long cylindersfabricated from abovementioned components. This evaluation was carriedout at the University of Memphis (Physics Department, Memphis, Tenn.).Free radical concentration was measured and calculated from an averageof three (3) specimens. Free radical measurements were performed usingelectron spin resonance technique. This is the only technique that candirectly detect free radials in solid and aqueous media. Atop-of-the-line ESR spectrometer (Bruker EMX) was used in thisevaluation.

Results and Discussion—The free radical concentration in the materialsis illustrated in Table 8; the measurement unit given is spins per gram(spins/g). The DCM Scorpio® PS tibial inserts subjected to the 2× (4.5MRads) sequential cross-link processes showed a significant reduction infree radical concentration of 97% when comparing to a Scorpio® PSmachined from compression molded GUR 1020 that received a 3.0 MRads ofgamma-radiation sterilization in a container with less than 0.5% oxygen.

TABLE 8 Free Radical Reduction in Free Concentration Radical Treatment(10E+14 spins/g) Concentration (%) Scorpio ® PS machined from 325 ± 28NA compression molded GUR 1020, received 3.0 MRads in a container withless than 0.5% oxygen (a reference material) DCM Scorpio ® PS GUR 1020 9± 0 97 received 2X (4.5 MRads) sequentially cross-link and annealed, 9.0MRads total

Example XI Effect of Sequential Cross-link Dose on the OxidationResistance of Direct Compression Molded UHMWPE Tibial Inserts

Materials and Methods—The materials for oxidation resistance evaluationare the same as the wear test materials described in Example IX, above.An accelerated aging protocol per ASTM F 2003 (5 atm oxygen pressure at70° C. for 14 days) was carried out at Howmedica Osteonics (Mahwah,N.J.). The specimens were machined and sequentially cross-link 2× (4.5MRads) DCM Scorpio® PS tibial inserts. The oxidation analysis wasperformed on a Nicolet model 750 Magna-IR™ spectrometer per ASTMF2102-01 using an aperture 100 μm×100 μm and 256 scans. An oxidationindex was defined by the ratio of the carbonyl peak area (1660 to 1790cm⁻¹) to the 1370 cm⁻¹ peak area (1330 to 1390 cm⁻¹). Athrough-the-thickness (about 6 mm) oxidation index profile was generatedfrom an average of three (3) specimens. The 0 and 6 mm depthsrepresented articulating and back surfaces of specimens. The maximumoxidation index of each specimen was used to determine if there was asignificant difference.

Results and Discussion—Oxidation index profiles and the maximumoxidation index are illustrated in FIG. 2 and Table 9, respectively. TheDCM Scorpio® PS tibial inserts subjected to the 2× (4.5 MRads)sequential cross-link processes showed a significant reduction in anoxidation index profile and maximum oxidation index. The sequentialcross-link process reduced the maximum oxidation index in 2× (4.5 MRads)DCM GUR 1020 Scorpio® PS tibial inserts by 90% when comparing to aScorpio® PS machined from compression molded GUR 1020 that received a3.0 MRads of gamma-radiation sterilization in a container with less than0.5% oxygen (see Table 9 below).

TABLE 9 Treatment Maximum Oxidation Index Scorpio ® PS machined from3.10 ± 0.03 compression molded GUR 1020, received 3.0 MRads in acontainer with less than 0.5% oxygen (a reference material) GUR 1020received 2X (4.5 MRads) 0.30 ± 0.02 sequentially cross-link andannealed, 9.0 MRads total

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

1. A medical implant with improved wear resistance irradiated to apredetermined total radiation dose of between and 10 MRad comprising anultra high molecular weight polyethylene (UHMWPE) cross-linked in asolid state at least three times by irradiation carried out at anincrement of the total dose to the predetermined total dose andthermally treated by heating at a temperature below the melting pointafter each incremental irradiation followed by cooling after eachheating, the irradiated material having an ultimate tensile strength of54.8±1.2 MPa.
 2. The implant as set forth in claim 1, wherein threeradiation doses are applied with an incremental dose for eachirradiation being between about 2 and about 3 MRad.
 3. The implant asset forth in claim 1, wherein the polyethylene has a weight averagemolecular weight of greater than 400,000 before cross-linking byirradiation.
 4. The implant as set forth in claim 1 wherein the freeradical content is 12±1 (10¹⁴ spins/gram).
 5. The implant as set forthin claim 1 having a yield strength of 25.6±0.04 MPa.
 6. The implant asset forth in claim 1 having a crystallinity of 58±0.9 percent.
 7. Theimplant as set forth in claim 1 wherein the wear rate is 1.4=³ permillion cycles.
 8. A preformed material for a medical implant comprisingUHMWPE sequentially crosslinked at least three times by irradiationcarried out at an increment of a total dose of 9 MRads, each irradiationfollowed by heating below the melting point and then cooling, theresultant material having a crystallinity of 58.0±0.09 percent and anultimate tensile strength of 54.8±1.2 MPa.
 9. The preformed material asset forth in claim 8 wherein the heating is at a temperature of between110° C. and 135° C.
 10. The preformed material as set forth in claim 8wherein each irradiation is at a dose between about 2 and 3 MRad.
 11. Amedical implant with improved wear resistance comprising an UHMWPEcross-linked at least two times by irradiation in the solid state inincrements of a total dose and heated at a temperature below the meltingpoint and then cooled after each irradiation wherein the total radiationdose is between about 6 to about 9 MRad and the irradiated preformedmaterial has an ultimate tensile strength between 57.2±3.9% and54.8±1.25 MPA.
 12. The implant as set forth in claim 11, wherein threeradiation doses are applied with an incremental dose for eachirradiation between about 2 and about 3 MRad.
 13. The implant as setforth in claim 11, wherein the polyethylene has a weight averagemolecular weight of greater than 400,000 prior to irradiation.
 14. Theimplant as set forth in claim 11, wherein the polyethylene is cooled toroom temperature for each irradiation.
 15. The implant as set forth inclaim 11, wherein the polyethylene is cross-linked three times byirradiation and heated after each irradiation at a temperature between25° C. and 135° C. for at least 4 hours.
 16. The implant as set forth inclaim 15 wherein the temperature is between 110° C. and 130° C.
 17. Theimplant as set forth in claim 1 wherein the heating is at a temperatureof 110° C.-130° C. for at least about 4 hours.
 18. A medial implant withimproved wear resistance comprising irradiated UHMWPE having an ultimatetensile strength of 54.8±1.2 MPa, a free radical content of 12±1 (10¹⁴spins per gram), a wear rate of about 1.4=³/million cycles and acrystallinity between 57.4±0.6% and 58.0±0.9%.
 19. The implant as setforth in claim 18, wherein the polyethylene has a weight averagemolecular weight of greater than 400,000 before cross-linking byirradiation.
 20. The preformed material as set forth in claim 18 havinga yield strength of 25.6±0.04 MPa.
 21. A medical implant with improvedwear resistance comprising: an ultrahigh molecular weight polyethylene(UHMWPE) irradiated between 4 and 10 Mrads followed by annealing theirradiated and annealed UHMWPE having a free radial concentration and anultimate tensile strength not significantly different (p<0.05) than anUHMWPE irradiated to about 3 Mrads in an atmosphere of less than 1%oxygen and not subsequently annealed and the irradiated and annealedUHMWPE having a wear rate reduced by greater than 86% when compared to awear rate of the UHMWPE irradiated in less than 1% oxygen and notsequentially annealed.